Journal
CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 4, Issue 12, Pages 1289-1310Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568026043387935
Keywords
aryl hydroxamic acids; aryl hydroxamates; MMP inhibitor; TACE inhibitor; anthranilic acid
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Three different classes of aryl hydroxamic acid scaffolds have been explored and provided potent inhibitors of MMP-1, -2, -9, -13 and TACE. Structure-based design has allowed the evolution of these inhibitors from broad spectrum inhibitors into compounds that are more selective for MMPs relevant to particular disease states. Aryl hydroxamates selective for MMP-9, MMP-13 and TACE have been disclosed that may aid in the study of the physiological role of these enzymes. Furthermore, the different selectivity profiles offered by these MMP/TACE inhibitors may allow the determination of which metalloprotease, or group of metalloproteases, must be inhibited for the safe, long-term treatment of osteoarthritis, rheumatoid arthritis and cancer. Sonic of these compounds have demonstrated useful biological activity in efficacy models relevant to osteoarthritis and rheumatoid arthritis and are therefore potential clinical candidates.
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